HRPP Blog

Risk - Part I

2011-01-31T09:05:00.000-05:00

Risk, one of the central issues in research ethics, is one of the most misunderstood and misapplied terms in the entire field of human research protections. This will be a two-part discussion of risk. This first part will deal with the misunderstanding with regard to the evaluation of risk in research. The second part will misunderstandings about the role of risk in human research protections.

Most researchers and most IRB members confuse risk and harm. Risk is not harm, risk is the possibility of harm. The evaluation of risk requires evaluation of both the magnitude and the likelihood of possible harm. To quote the Belmont Report, “The term "risk" refers to a possibility that harm may occur. However, when expressions such as "small risk" or "high risk" are used, they usually refer (often ambiguously) both to the chance (probability) of experiencing a harm and the severity (magnitude) of the envisioned harm.” The federal regulations do not define risk; however, in defining “minimal risk” the regulations state, “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”

Most protocols merely list the possible harms that might occur in the research. For example, a research protocol might list hair loss as a risk. This tells us nothing about the risks of this research. In order to evaluate the risk of hair loss, we need to know the severity of the hair loss and the likelihood of the hair loss occurring. A remote chance of slight hair loss is very different from the likely loss of all of one’s hair. IRBs must determine whether the risks are reasonable in relation to the benefits of the research. Most people would consider a high likelihood of total hair loss a reasonable risk in an oncology study but not in an acne study.

In addition to IRBs needing this information, subjects need this information to decide whether to participate in the research. A remote chance of slight hair loss may be a minor risk to most people, but to a teenage girl, the research would probably have to have significant benefit to justify that risk. The subjects must be provided information on both the magnitude and the likelihood of the possible harms in order to give true informed consent. This information must be provided to the subjects in language that they can understand and evaluate in terms of their own lives and values. As with the protocols, most consent forms merely list possible harms without provide real information about the risks of research.

This concern is not limited to biomedical research. The same requirement applies to social/behavioral research. Much social/behavioral research is “minimal risk,” but to make that determination, the IRB must examine both the magnitude of the possible harm and the likelihood that the harm will occur. Consider, for example, a survey on AIDS and substance abuse. While the magnitude of the possible harm if the information was inappropriately divulged is great, in order to evaluate the risk the IRB must also evaluate the likelihood of that occurring. If the confidentiality procedures were sufficient to ensure that there is an extremely small likelihood of the information being divulged, then the research might be considered a minimal risk study.

So, IRBs need to have information about both the magnitude of the possible harm and the likelihood of the harm occurring in order to determine if the risks are reasonable in relation to the benefits. If the IRB does not have enough information on both of these, it cannot approve the research.

Answering Questions

2010-12-11T15:41:00.001-05:00

Before I get into the topic of this blog, I want to apologize, once again, for my sporadic posting. Our consulting firm (HRP Consulting Group) has been undergoing considerable growth and change over the past year and I have not had the time to devote to keeping up with blogging. I want to assure any readers that I have left that I am now committed to maintaining this blog. In fact, I have asked my colleagues in the firm to nag me on a regular basis about this! In this blog I will continue to share my thoughts and comments on the HRPP field, but, from time to time, I may turn this space over to my colleagues (Cheryl Savini and Nick Slack) when they have interesting thoughts they would like to share.

And now for my topic of the day – answering questions. I just got back from a very exciting PRIM&R meeting. While at the meeting, I conducted a few workshops where there were lots of questions asked and I was asked lots of questions in the hallways and at our booth. This caused me to think about what it means to answer questions in our field, and I thought I’d share my thoughts about this.

First of all, I do not believe that there are any “right” answers to questions in our field. Nothing in human research protections is black or white; it is all gray. Everything is open to interpretation, even the regulations. And the only wrong answers are those that are clearly in violation of the regulations. So, when I answer a question, my answer is my opinion, based my years of experience and my interpretation of the regulations and best practice. For example, I was asked several questions about “quorum” at IRB meetings. The regulations at 45 CFR 46.108(b)/21CFR 56.108(c) say: “Except when an expedited review procedure is used, [each IRB shall] review proposed research at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in nonscientific areas. In order for the research to be approved, it shall receive the approval of a majority of those members present at the meeting.” This may seem straight forward, but there is plenty that is open to interpretation. What is a majority? What is a nonscientist?

My answer will reflect my opinion on how best to meet the spirit of the regulations and implement practical procedures for ensuring the maintenance of a quorum. So, I would suggest a “simple majority” which is more than half of the members (for example, if there are 9 members 5 would be a majority). A nonscientist should be someone who clearly has no scientific training or experience; if there is any doubt, then that person is not a nonscientist. And, institutions should not rely solely on the unaffiliated member to be the nonscientist since it is sometimes hard to get the unaffiliated member to a meeting. Could someone else come up with a different answer? Certainly! Is my answer the “right” one? There is no one “right” answer but my answer will not be a “wrong” answer. If I give you an answer to a question, you should see it as my expert opinion and weigh how well it works for you and your circumstances.

Second, there is almost always more than one way to accomplish regulatory and ethical goals in our field. What works at one institution may not work at another. People should get as many opinions as possible on a given issue and choose the one that works best for them. For example, in a study on heroin use, subjects may reveal information about other people (dealers, fellow users, etc.). Under the regulations these people may be considered subjects because identifiable, private information is being obtained. How is the IRB to deal with these “secondary” subjects? One institution may require informed consent from these people. Another may require that they be de-identified and another might have the IRB waive the requirement for informed consent if the confidentiality procedures are sufficient to say that is a minimal risk study. When I am answering a question I will always try to give options and, even if I don’t, there are always other options available.

Finally, the federal regulations are the “floor,” not the “ceiling.” They set minimum standards and specify the least that you can do, not what you should do. A good human research protections program should not be based only on compliance with regulations, but also based on best practice. Institutions have been working with these regulations for almost 40 years and have figured out good ways to implement them in ways that protect subjects while continuing to facilitate research. For someone to say, “This is what it says in the regulations and that’s what you should do,” ignores best practice and the need for higher standards. And, once you get into the area of best practice, you leave the realm of right and wrong.

So, am I saying that my answers are not useful because they are not definitive or “right”? No, I think my knowledge of the regulations and my over 30 years of experience in the field give some weight to my answers. However, don’t expect me to tell you what is “right”.

OHRP Guidance on Exemption Determinations

2009-10-21T01:42:00.002-04:00

OHRP has come up with new guidance on exemption determinations (http://www.hhs.gov/ohrp/policy/exempt_res_det.html).

Although OHRP continues to recommend that investigators not be given the authority to independently make these determinations, they are more explicit in indicating that, under the regulations, institutions can adopt a policy that allows investigators to make their own exemption determinations. OHRP even gives examples of procedures which allow investigators to determine that their research is exempt, begin the research and then have the determination reviewed by an appropriate institutional office.

However, allowing investigators to make exemption determinations increases the likelihood that non-exempt research would be inadvertently conducted without IRB approval. This not only puts subjects at risk, but also puts the institution and the investigator at risk of non-compliance.

This guidance will likely be interpreted by investigators as blanket permission by OHRP for investigators to decide that their research is exempt without needing any other review. Institutions are advised to come up with a clear justification as to why investigator exemption determinations are not in the best interest of subjects, the institution or even the investigators.

While no one is questioning the ethics or integrity of investigators, they should not make these determinations for the following reasons:

1) No one can be totally objective about their own work. While we all try to be objective, human nature makes difficult to see all of the implications of work that is very familiar to us. Also, we tend to underestimate the risks in very familiar activities. So, every research activity needs an independent, objective review to ensure that the investigator has not overlooked some important implications for subjects in the research they are proposing.

2) Although it is assumed that exempt research has minimal risk for subjects, that is not necessarily the case. Although it may be less likely in this type of research than other types, exempt research such as interviews and surveys can harm subjects and the determination of risk, especially social and psychological risks, is more difficult than it may seem. The individuals making the exemption determinations must have sufficient knowledge and experience to evaluate the risks.

3) The exemption categories in the regulations are not as clear-cut as they may seem. Making an accurate determination with regard to whether research fits in a given category requires some training and experience with exemptions. Investigators generally do not have that level of experience.

We believe that investigators should not have the authority to determine whether their own research is exempt. That being said, it is incumbent on institutions that do not allow investigators to make exemption determinations to come up with determination procedures that are minimally burdensome and expeditious. Exempt research is generally innocuous and often time sensitive.

The exemption determinations do not have to be made by the IRB or even the IRB office, but the individual(s) making the determinations must be knowledgeable about the regulations and ethical principles. The institution must provide some sort of oversight over the process to ensure that accurate determinations are being made.

The process for requesting an exemption determination should not require investigators to fill out extensive forms. The reviewer does not need all of information that is needed for non-exempt research, only enough to make an accurate determination.

The process should also be as quick as possible. These are determinations that can be made in days, not weeks and often on the spot. Whoever is making the determinations should be readily available and provide quick turnaround.
Finally, a word to the wise with regard to OHRP’s examples of investigator determination policies , OHRP considers the conduct of non-exempt research without IRB approval as non-compliance. If, under OHRP’s examples, an investigator makes an exemption determination, begins the research and then an institutional review determines that it is not exempt, the conduct of that research prior to the institutional review would be non-compliance and would have to be reported to ORHP. We have confirmed this with OHRP.

Substantive IRB Review

2009-06-23T03:00:00.000-04:00

With all of the attention and increased oversight of IRBs, it is essential that organizations ensure that all IRB review is "substantive". In the past, and all to often even now, IRBs have used what could be called the "sniff test". You know when you have a container of milk in the fridge and you don't know how long it's been there, you pick it up, smell it and, if it smells OK, you drink it. Well, that's how a lot of IRBs review protocols. They look at the research and, if it's good science and they are getting consent, they approve it. That's not substantive review.

The regulations have always been very specific about what constitutes substantive review. Section 111 of the regulations (in both the Common Rule and FDA regulations) details the Criteria for IRB Approval of Research. Section 111 states: "In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied". The criteria in Section 111 include: risks are minimized, risks are reasonable in relation to benefits, subject selection is equitable, informed consent is appropriately obtained, informed consent is appropriately documented, data monitored to ensure subject safety, privacy and confidentiality are protected, and additional protections are in place for vulnerable subjects. Substantive IRB review means that each and every one of the criteria are addressed by the IRB for every review - initial review, continuing review, and review of modifications.

In addition to the 111 criteria, there are also other required determinations in the regulations, such as the criteria for waiver of consent and the use of vulnerable popultions. These too, when applicable, must be addressed by the IRB.

Most IRBs that do more than the "sniff test" sort of address the 111 criteria and other required determinations, but don't do it in a systematic way. The best way to ensure that the required determinations have been addressed is to use a review checklist which includes all of the required determinations. Many IRBs have review checklists but don't really use them. Individual reviewers should use the checklists when doing their review and the full IRB should use the checklist to guide it's discussion of the research.

Of course, as they say, "It's not good enough to do the right thing, you must also be able to demonstrate to others that you have done the right thing." It's not enough for IRBs to address the required determinations, they must also adquately document that they have addressed them. For full IRB review, the minutes should document that the IRB addressed the 111 criteria for each protocol and the other required determinations as applicable. For expedtied review, there should be a review form that documents that they are addressed and is signed by the reviewer.

By ensuring that the IRB is doing a substantive review and adequately documenting that it has been done for every review, an organization not only fulfills it's responsiblity under the regulations, but also best protects itself from outside criticism or worse.

OHRP Proposes New IRB Rule

2009-04-23T07:31:00.002-04:00

ORHP has issued an Advanced Notice of Proposed Rule Making to enable OHRP to hold institutional review boards (IRB) and the institutions or organizations operating the IRBs directly accountable for meeting certain regulatory requirements of the DHHS regulations for the protection of human subjects. (http://edocket.access.gpo.gov/2009/E9-4628.htm) Comments on this proposal are due by June 3, 2009.

If adopted, this proposal could change the relationship between research institutions and external IRBs. Is this a good thing or not? Although I think that external IRBs should be held accountable for compliance, I am concerned that this will make some of the problems concerning external IRBs worse. One problem with external IRBs is what was illustrated with the GAO sting. Research organizations just pick an IRB without making sure that they meet appropriate standards. If the organizations are no longer responsible for IRB compliance, this will increase the likelihood that organizations will just pick an IRB that is fast and easy. Second, organizations that use an external IRB often do not realize that they need to have an HRPP and oversee the research. They think they have IRB approval so that's all they need to do. This new rule could increase that tendency.

So, I think that holding external IRBs accountable is fine, but OHRP should continue to hold the research organizations accountable for IRB compliance as well.

Accountability: Preserving Public Trust

2009-04-22T12:08:00.001-04:00

Human research protection programs primarily focus on ethics and regulatory compliance. However, those are not the only functions of HRPPs; they also serve to preserve public trust in research. We must remember that there is no right to conduct research. Research, especially research involving human subjects, is a privilege granted to the research community by the public. That privilege is granted based on the trust that the research will be conducted according to appropriate ethical principles and regulations. Anything that erodes that trust can result in that privilege being restricted or withdrawn. When the public has serious concerns about research it puts pressure on Congress and federal agencies to further regulate research, which is how we got to the current regulatory situation in this country.

So, how do HRPPs serve to maintain the public trust in human research? Through accountability; that is, being able to demonstrate that organizations and investigators are conducting research according to ethical and regulatory standards. It is not good enough just to do the right thing; we must be able to demonstrate to others that we are doing the right thing!

Accountability begins with investigators and institutions maintaining appropriate documentation. If you examine the federal regulations you will see that, although part of the regulations address the implementation of ethical principles (informed consent, risk/benefit, etc.), the rest is about documentation (consent forms, minutes, etc.). This is because the regulations, when they were drafted, were designed to restore public trust in human research.

The next level of accountability involves oversight by government agencies. The federal human subject regulations were first imposed back in the 70s because the public trust in research had eroded. When public trust eroded again in the mid-90s, federal oversight increased. By issuing regulations and overseeing the compliance with those regulations, the government assures the public that human research is being conducted with appropriate safeguards for the rights and welfare of subjects.

Finally, accountability involves accreditation. Organizations must be able to demonstrate that they have an HRPP that meets appropriate standards. An independent accrediting body, currently AAHRPP, develops HRPP standards and assesses organizations as to how well their HRPP meets those standards. Accreditation involves more than just compliance with regulations and appropriate documentation; it also involves the evaluation of the effectiveness of the HRPP through a site visit and interviews. As more organizations become accredited, the public can trust that research at those institutions at least meets AAHRPP standards.

Many people in our field see accountability as just so much bureaucratic nonsense and fail to appreciate the important role it plays in ensuring that important research can continue to be done. Maintaining the public's trust in research is as important as the ethical conduct of research for, without that trust, the conduct of research will be even more difficult.

IRB Stings & Accreditation

2009-04-22T12:05:00.001-04:00

The IRB world has been rocked by the recent "stings" conducted by the Congressional Government Accountability Office (GAO) to investigate IRBs. This investigation was conducted at the behest of Congress because of concern over the adequacy of IRB review. Those who are not familiar with the results of the investigation should review the GAO and testimony from the hearings:
http://energycommerce.house.gov/index.php?option=com_content&task=view&id=1552

Although the focus of the hearings was on Independent IRBs and most of the attention has been on Coast IRB, the concerns raised by this investigation and these hearings apply to the whole field of human research protections. The best response to this investigation is accreditation. Accreditation not only raises the standards for what constitutes adequate IRB review, it provide helps ensure that organizations are meeting those standards. How would accreditation have addressed the GAO findings in this investigation?

1) Due diligence to verify information

The GAO faked 510(k) status of the device and the qualifications of PI. AAHRPP expects IRBs to obtain documentation of INDs, IDEs and 510(k) status. AAHRPP also expects organizations to have an ongoing quality assurance program, which should include audits and site visits.

2) Inadequate information to make determinations

The GAO selected IRBs that "...had less burdensome initial paperwork requirements than other IRBs for protocol submission" and "...designed our protocol so that it would contain vague information about certain aspects of our proposed study." AAHRPP expects detailed information in the protocol on all aspects of human subject protections, including subject populations, subject recruitment, consent process and safety monitoring. If the protocol requirements had been that detailed, the GAO could not have provided the information.

3) Lack of substantive IRB review

The GAO raised concerns that one IRB approved the protocol even though there were safety concerns. AAHRPP expects that all IRB review will be substantive and will address all of the regulatory criteria for approval for each review. This must be documented in the minutes with protocol-specific justification that the criteria have been met.

4) Inadequate federal oversight

The GAO was able to register a fake IRB and get an assurance for a fake medical device company. Beyond assuring that the minimum regulatory requirements have been met, OHRP is unable to review the quality of IRBs or research institutions. Accreditation will provide the accountability to help ensure that there is adequate IRB of human research.

The best protection that institutions and IRBs have against the kind of investigation conducted by the GAO (and, for that matter, against litigation) is accreditation. Not only will AAHRPP accreditation help ensure adequate IRB review, but organizations will be able to say, "We're doing it right and you don't have to take our word for it!"

Posts from Newsletter

2009-04-22T11:31:00.002-04:00

We have sent out three newsletters so far (they are available in the Newsletter Archive: http://archive.constantcontact.com/fs039/1102478511527/archive/1102495502466.html). In the newsletter we have included articles and discussions which should be of general interest to the HRPP community so we will be copying them here on the blog. This will also allow ongoing discussion on these topics.

Doing More With Less

2009-04-22T11:26:00.002-04:00

As we all know, we are living in difficult times. Those of us in the human research protections field are faced with the challenge of maintaining an appropriate level of protection with diminishing resources. Here are some ways that institutions can "do more with less":

Increase Efficiency

Review policies and procedures to evaluate efficiency
Track the "life of a protocol" to look for bottle-necks and unnecessary steps that can be eliminated without compromising the quality of IRB review
Automate processes to save steps and time

Reduce Waste, Save Time

Make full use of the flexibiltiy available in the regulations. No need to take up IRB time for research that is exempt or eligible for expedited review
Poorly prepared protocols waste staff, IRB and investigator time

Improve forms to ensure that IRB receives all the necessary information
Improve investigator education and guidance to obtain better protocols

Cope with Staff Reductions

Computerized IRB System

Equivalent of at least .5 FTE

Outsource IRB functions

Quality Assurance
Education and Training

Webinars

Full IRB Administration

Use an external IRB

HRPA Newsletter

2009-03-09T07:07:00.002-04:00

For those of you who are reading this blog, I want to apologize for not keeping it up. In this busy life, it's just something that slips through the cracks. I will try to do better in the future. In the meantime, I want to refer you to the HRPA Newsletter. It not only talks about what our consulting firm is up to, it will also provide articles of interest to people in the human research protections field, a Q&A section where we answer questions sent to us and news relating to HRPPs.

PRIM&R Thoughts

2008-11-21T10:04:00.003-05:00

Just back from PRIM&R in Orlando. It was a fantastic meeting; one of the best yet. The theme of the meeting was one that resonated with me because it is a theme that I have been stressing for almost 30 years - balancing the needs of human subjects and science. I have been saying for years that the role of the IRB is not to protect subjects but to facilitate ethical research. The IRB does that by balancing these two social concerns - the rights and welfare of human subjects and the need to advance science and human understanding.

One way to help achieve that balance is for IRBs to understand and use the flexibility in the regulations. The regulations give the IRB considerable flexibility and authority to effectively and efficiently conduct reviews that are appropriate to the research and not impose unreasonable burdens on researchers. Why don't some IRBs utilize the flexibility in regulations? As Kristina Boror, Director of the Division of Compliance Oversight at OHRP, said at a workshop on flexibility at PRIM&R, some of the reasons include:
- Ignorance of regulatory flexibility
- Fear of making the wrong decision
- Fear of OHRP or other compliance oversight determination
- Mistrust of reviewers or investigators

So, the first thing is for IRBs to understand the flexibility in the regulations. IRBs have flexibility with regard to the definition of human subjects research, determining exemptions, using expedited review and waivers of informed consent and/or documentation of consent. IRBs should understand how to use these flexibilties withing the parameters of the regulations.

Many IRBs are afraid to use the flexibility because they are afraid that they will be "shut down" for making the wrong decisions. Our former boss at OHRP, Greg Koski, coined a term for this - "reactive hyper-protectionism". Fear of regulatory oversight causes rigidity in applying the regulations. This is not what the regulations intend and it is not what OHRP or FDA intend. The regulations were written so that IRBs would use the flexibility and OHRP and FDA expect IRBs to use the flexibility. As long as the IRBs understand the parameters in place for using the flexibility and stay within those parameters, the feds are not going to second guess them. Also, institutions do not get "shut down" for individual decisions, they might get criticized by OHRP or FDA, but they only get "shut down" for system-wide failure to adequately protect subjects.

Then there is mistrust of investigators and reviewers. If the IRB is flexible, then the investigators will "get away with murder" (an actual comment I got from IRB members at an institution I was consulting for) and IRB reviewers will not do a substantive review. Well, this relates to the Belmont principle of respect. IRBs need to respect their investigators and reviewers and appreciate that they generally want to do the right thing. As long as the IRB has clear written policies and procedures, so that investigators and reviewers know the parameters of the flexiblity and how to apply it, then IRBs can trust the process and don't need to be "hyper-protectionist".

Finally, Ivor Pritchard, in his keynote address at PRIM&R, pointed out the risk of inconsistency inherent in flexiblity. This is a real risk and IRBs need to vigilent in making sure that, in applying the flexiblity, they remain reasonable consistent in the review process. The best way to do this is to have clear written policies and procedures so that the flexiblity is consistently applied.

In closing, I want to reiterate what I have been saying for some time. An IRB that is overly rigid in applying the regulations and does not use the flexibilty in the regulations is not living up to its mission and, by imposing unreasonable and unnecessary burdens on investigators, is actually doing harm to subjects and human welfare.

Ethics & Regulations

2008-10-21T07:09:00.004-04:00

One of the talks that I often do is entitled, "Ethics & Regulations in Human Subjects Research". Once, when I was about to start the talk, a researcher yelled out, "That's an oxymoron. Regulation doesn't have anything to do with ethics." Well, I can't talk for all regulation, but, with regard to the human subjects regulations, that's not true.

The basic ethical principles underlying research involving human subjects are contained in the "Belmont Report" and they are Respect for Persons, Beneficence, and Justice. Although some argue that these principles are not applicable to all research, I don't agree. I've been involved in the human research protections field for almost 30 years and have seen all kinds of research and I am absolutely convinced that these principles apply to all research, if not to life in general. I challenge anyone to explain to me how they might not apply.

However, these are abstract principles. How do we apply them to the review of research to help ensure that the research is being conducted ethically? That was the challenge facing the drafters of the regulations. The solution was Section 111 of the regulations (45 CFR 46.111 and 21 CFR 56.111) - The Criteria for IRB Approval of Research. The "111 Criteria", as they are called, take the abstract principles of the Belmont Report and turn them into criteria that can be used to evaluate whether research is being done ethically. The criteria in Section 111 include: risks are minimized, risks are reasonable in relation to benefits, subject selection is equitable, informed consent is appropriately obtained, informed consent is appropriately documented, data monitored to ensure subject safety, privacy and confidentiality are protected, and additional protections are in place for vulnerable subjects. These criteria are directly related to the Belmont Principles: risk/benefit analysis and subject safety - Beneficence, equitable subject selection - Justice, informed consent, privacy/confidentiality, and protection of vulnerable subjects - Respect for Persons.

So, by applying the 111 Criteria, IRBs are implementing the Belmont Principles and conducting ethical review of research.

Human Nature

2008-10-07T20:15:00.002-04:00

Many of the critics of IRB review in the social sciences argue that they don't need IRB review because individual researchers are ethical and will make sure that their research meets the appropriate ethical standards. The flaw in this argument is human nature. One of the things that we know about human nature is that no one can be totally objective about their own work. We can and must try to be objective about the risks and benefits of our research, but we can't be totally objective. One way that we're not objective is that we all tend to underestimate the risks of things with which we are most familiar. I often use the example of the time I got in a cab to go to the airport and the cab was in a minor accident. I hit the plastic behind the driver, banged my nose and bit my lip. I wasn't wearing a seat belt. Why? Because I was underestimating the risk of that part of my trip. Living in New York City, I take cabs all the time and it was that familiarity which led me to underestimate the risks. It's the same in research. We can't be objective about the risks in the procedures or situations that are most familiar to us. We also overestimate the benefits of our work. If we didn't think that what we were doing was important, we wouldn't get out of bed in the morning to do it.

As I said in my previous post, ethical research requires that the risks of the research are identified, that the risks are minimized, and that the risks are reasonable in relation to the potential benefits of the research. Although researchers have the primary responsibility to make that analysis, since they can't be totally objective about the risks and benefits, every research activity needs an independent, objective review. That is what the IRB is supposed to provide. The IRB, however, must also be objective and have the necessary expertise to make this risk/benefit analysis.

Risk - Part 2

2008-09-29T07:01:00.001-04:00

In addition to identifying risks, IRBs must ensure that the risks are minimized, that the risks are reasonable in relation to the anticipated benefits, and that subjects are informed about reasonably foreseeable risks.

Minimizing risks does not mean eliminating risks. There is nothing in the Belmont Principles or the regulations that requires that research be risk free. Research sometimes involves risk to subjects. Research ethics demands, however, that the risks be the minimum necessary to obtain valid results. No researcher wants to subject people to unnecessary risks. Researchers, though, need to actively consider whether the risks in their research are actually minimized. How do we minimize risks? One way is to explore alternatives – is there another way to do this research that would be less risky? A second way to minimize risk is to add precautions to the research. These are procedures that reduce the likelihood that the harm will occur, such as additional screening or subject preparation prior to the research. Sometimes, however, the risk in the research is unavoidable. In this case, researchers need to build in contingencies that will reduce the impact of the harm when it occurs, such as increased monitoring.

Analyzing the risk/benefit relationship is one of the key components of research ethics. It is not ethical under any circumstances to inflict risk on subjects unless those risks are justified by the benefits that are expected to accrue from the research. Even the most zealous scientist would not engage in research that might harm subjects unless there was some good which could come from the research. The more risky the research, the more benefit it takes to justify that risk. Not all research, however, must involve direct benefits to subjects. Although the regulations talk about risk to subjects, benefits may be to subjects or others. Advancing scientific knowledge or improve social welfare are benefits; even training students is a benefit. Direct benefits to subjects, however, are stronger benefits than benefits to others and, therefore, more risks are justified.

Finally, it is required that subjects be informed about the risks and benefits of the research. These need to be described to subjects in a way that they can understand and make an informed decision as to whether these are risks they are willing to take. As I said in my first post on risk, simply listing the possible harms in a research study is not informing subjects about the risks.

To sum up, risk is a very misunderstood and misapplied term. We must make sure not to confuse risk and harm and remember that simply listing possible harms is not informing subjects about the risks in research. We must also make sure that the research involves the least amount of risk necessary to obtain valid results, that the risks are justified by the benefits of the research and that subjects are clearly informed about the risks and benefits of the research. Only then will we, researchers and IRBs, be fulfilling our ethical responsibility to the subjects of the research.

Risk - Part 1

2008-09-23T17:34:00.000-04:00

Risk is one of the central concepts in human research protection and is one of the most misunderstood and misapplied terms in the field. Many IRBs and investigators treat risk as if it were the same as harm to subjects, which is why the IRB Forum had a recent discussion about the use of the phrase “possible risk” in consent forms. Risk is not harm; risk is an estimate of the magnitude and probability of the harm to subjects that might happen in research. “Your hair might fall out” or “you might go blind” are not risks, they are possible harms. Simply telling subjects that one or both of these might occur is not informing them of the risks.

In order to determine the risk of these events, you need to evaluate both the severity of the possible harm and the likelihood that the harm with occur. A very severe harm that is extremely unlikely to occur may be a minimal risk, while a less severe harm that is very likely to occur may be more than minimal risk. Clearly, the possibility of going blind is a very serious harm, but if the chances that it will happen are one in five million, then it may be a minimal risk that subjects are willing to take. Losing hair, for most people, is not a very serious risk, but if it is a sure thing, I might have second thoughts about it.

To inform subjects about risks, IRB and investigators must evaluate the risks and make sure that subjects are informed about the reasonably foreseeable risks in the research. This means that IRBs must identify the possible harms in the research, evaluate both the magnitude and probability of those harms, and make sure that subjects are given adequate information about what harms might occur and the likelihood that they will occur. Again, simply listing possible harms is not informing subjects about the risks in the research.

In fact, just providing subjects with a long list of possible harms not only doesn’t inform them about the risks, it is “disinformation”. When subjects see that list of harms, which in some cases goes on for pages, they tend to discount all of it and don’t pay attention to the real risks in the research that they need to focus on to decide whether to participate in the research. Consent forms that include such a “laundry list” of harms without indicating which are likely to occur and which are less likely, are not in compliance with the regulations and should not be approved by IRBs. If sponsors insist on using such consent forms, IRBs should require other mechanisms to explain the real risks to subjects, such as oral presentations and information sheets.

Informing subjects about risks is not the only responsibility with regard to risk that IRBs have; they must also ensure that the risks are minimized and that the risks are reasonable in relation to the anticipated benefits of the research. I’m going to discuss those two responsibilities in another posting.

Checklists

2008-09-09T07:40:00.002-04:00

Checklists have gotten a bad rap!! I, too, had a negative attitude toward checklists. It seems like they work against real ethical decision-making by IRBs. But, as I have been working with institutions going through accreditation (AAHRPP is big on checklists), my attitude has changed. I now see that, when used appropriately, checklists serve an important function in the IRB review process. Checklists don't ensure good IRB review, but they do help ensure that things don't "slip through the cracks". In order to do a good review, the IRB must carefully look at each of the criteria for approval in Section 111 of the regulations. Even the best IRB reviewer can miss something and review checklists help make sure that the reviewer considers all of the essential aspects of the criteria when doing the review.

You might say (and many do), that this is just a bureaucratic exercise to comply with regulations and does not do anything to better protect subjects. However, the criteria for approval in Section 111 implement the Belmont Principles (I'm going to do another post on that), so making sure that the review addresses all of the criteria ensures that the ethical principles are adequately addressed.

So, I've become a fan of good checklists, but they should be used as guidance not bureaucracy. It's not about checking off boxes, but about focusing the reviewer's attention on the important factors in ethical review.

Guidance Creep

2007-11-02T16:59:00.000-04:00

In a recent exchange with a colleague, he commented on what he called "Guidance Creep". He was referring to the situation where OHRP (or some other regulatory agency) responds to a question about an IRB practice and it is disseminated as "OHRP says..." which then becomes interpreted as OHRP guidance.

"Guidance Creep" is actually worse than "Regulatory Creep" since it is harder to refute. For regulatory creep, if it's not in the regs, it's not in the regs. But, with guidance creep, once something is seen as "best practice" it becomes what is expected in the field. Institutions have to remember that the only guidance that is "binding" is the official guidance that posted on the OHRP website. Unofficial opinions are not to be interpreted as guidance. Even with official guidance, it is still guidance. If an institution can make a good case for why deviating from the guidance adequately complies with the regulations and protects subjects, then they are free to do so. Of course, OHRP may not agree with the justification, but it rarely "second guesses" a reasoned justification.

This is also a problem with the accreditation process. I spend a lot of time with clients who are going through accreditation trying to distinguish between what's required in the regulations and what AAHRPP expects. When it is an AAHRPP expectation, the institution can decide if it works for them and, if it doesn't, push back. Of course, there is a risk to that if AAHRPP doesn't accept your argument, so the institution has to decide if pushing back is worth the risk. That, though, is a good thing since it requires that the institution really think through its practices and procedures and decide what's really important for human research protections.

All-in-all, it is important for institutions to seriously consider their policies and practices and not just blindly "comply with the regulations" or adopt OHRP or AAHRPP "guidance".

Privacy

2007-10-28T16:59:00.000-04:00

My last post was on confidentiality so I thought I’d write about privacy in this post. First of all, “privacyandconfidentiality” are not one word. Privacy and confidentiality are two different things. Unfortunately, most IRBs and investigators treat it as one thing and, when they address it at all, usually only address how data is being protected from disclosure. Also, because HIPPA is called the “Privacy Rule”, many IRBs and investigators feel that they are addressing privacy if they are complying with HIPPA.

Privacy means having control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with others, while confidentiality refers to the methods used to ensure that information obtained by researchers about their subjects is not improperly divulged. So, we invade someone’s privacy when we access them or their information without appropriate authorization. The problem is that privacy is a very ambiguous term, so it is often hard to determine when we’ve invaded privacy. The federal regulations [45 CFR 46.102(f)] give us some guidance on this. They define “private information” as “…behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).” Based on this, it is the context and the person’s reasonable expectation that determines privacy.

Some examples might help clarify when privacy might be considered to be invaded. One common procedure for recruiting subjects that meet certain enrollment criteria is for the investigator to access records, such as medical records or school records), select individuals who meet the criteria and contact them to recruit them for the research. Often subjects, when contacted in this manner, ask “How did you get my name?” indicating that the investigator has invaded their privacy. They provided the information in the record with a reasonable expectation that the information would be used for the purposes for which it had been given and not for research purposes. If, however, they had been informed when they gave the information that it might be used for research purposes, then they would not have a reasonable expectation of privacy.

Another recruitment procedure is to go up to people in a certain location and ask them to participate. Whether this constitutes an invasion of privacy depends on the circumstances. Going up to people in a mall or on the street is not a problem because their presence in that setting is not private. However, going up to people in an emergency room waiting area, at their hospital bed or in a public restroom would be an invasion of privacy. In these contexts, people have a reasonable expectation of privacy.

This brings up another issue related to privacy. When is behavior “public behavior”? In our society, not all behavior which occurs in public is “public behavior” and we can invade people’s privacy even when they are in public. For example, if you were walking down a street talking with a friend, you would naturally assume that the people around you could overhear your conversation. The fact that they overhear your conversation is not an invasion of privacy. However, if you turned around and a researcher was following you and writing down everything you said, you would feel that your privacy was invaded. While we expect people to casually overhear us, we don’t expect to be systematically recorded. This is similar to investigators studying online chatroom behavior who say that it is public behavior since anyone can access the chatroom. However, participants in a chatroom don’t reasonably expect that their conversations are going to be systematically recorded and analyzed. I would say that such research could be considered an invasion of privacy.

Of course, all of this depends on the nature of the research and the sensitivity of the information. There are many innocuous research studies where most people could care less whether the investigator has appropriate authorization to access them or their information.

So, protection of privacy is an important ethical issue in human subjects research, but privacy issues are more complicated than they seem. Investigators need to carefully consider the privacy interests of their subjects and IRBs need to ensure that the research adequately protects those privacy issues.

Confidentiality

2007-10-03T12:15:00.000-04:00

Confidentiality is a crucial topic in human subjects research. However, this is an area where some IRBs have gone overboard in applying the principle. Confidentiality is not some absolute principle that must be guaranteed in all research. Rather, confidentiality protection is based on risk. The degree of confidentiality protection is directly related to the harm that could befall subjects if the information is inappropriately divulged. The regulations make this clear when they say, in the criteria for IRB approval (Section 111, #7), that "When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data." Also, in the required elements of informed consent (#5) the regulations say that researchers must include "A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained," So, the regulations don't require confidentiality for all information in all research, only when it is appropriate. When is it appropriate? When the information, if it became know to others outside the research, could put the subjects at risk of harm. IRBs need to weigh the risk of harm from the information when deciding on appropriate confidentiality.

For some research there is no way that any of the information from could possible harm the subjects, even if it were to be divulged (such as innocuous surveys). For other research, the subjects expect or give permission for their identities to be divulged (such as some oral history research). In these cases, it is inappropriate for the IRB to require extensive confidentiality procedures. Some IRBs have even required anonymizing oral history narratives where the subjects want to have their story identified.

In other research, especially much biomedical research and some sensitive social science research, the information “could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation” as the regulations state in the exemption categories. In these cases, the IRB must carefully weigh appropriate confidentiality procedures to protect subjects. Here too, however, if subjects fully understand the consequences and agree to have their information identified, then IRBs should not impose severe confidentiality requirements.

On a related note, the risk when investigators gather sensitive information is not that the investigators have the information (the subjects have agreed to that), but that the information is inappropriately divulged. Therefore, even when extremely sensitive information is gathered in a study, if the confidentiality procedures are adequate to reasonably ensure that the information will not be inappropriately divulged, the research may still be no more than minimal risk. Some IRBs, when they see sensitive information gathered in study, immediately classify the research as more than minimal risk. This is inappropriate.

IRB Expertise

2007-10-02T09:18:00.000-04:00

One of the major criticisms of IRBs that are raised by unhappy with IRB review is the expertise of the IRB. IRB expertise is a crucial element in effective IRB review of research. The regulations, at §46.107(a) state: "Each IRB shall have at least five members, with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution. The IRB shall be sufficiently qualified through the experience and expertise of its members, and the diversity of the members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. In addition to possessing the professional competence necessary to review specific research activities, the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. The IRB shall therefore include persons knowledgeable in these areas." Therefore, an IRB that reviews a research study without the necessary expertise is not in compliance with the regulations. If it does not have that expertise on its membership, then it must use consultants to advice it.

The reason that the regulations, and best practice, requires appropriate expertise is that one cannot evaluate the risk in a research project unless one has expertise in that research area. The reviewers need to know the scientific background of the research and be knowledgeable about common practice and experience in the field.

When I was at the medical college, the IRB, which was primarily made up of health care professionals, received a qualitative, social science project to review. The IRB promptly disapproved it because it wasn't "science" in the view of the IRB members. I told them that they didn't have the necessary expertise to even review the project and had the research sent out to consultants with expertise in qualitative research. The IRB, after taking into account the reviews by the consultants, ultimately approved the project. This is an appropriate action by an Institutional Official. I did not overrule the decision by the IRB, but I made sure that the research was approved appropriately.

The same thing can happen when a social/behavioral IRB is made up of quantitative researchers, such as psychologists and sociologist and reviews an anthropology or oral history study.

It is the responsibility of the Chair and the IRB staff to determine whether the reviewers have the necessary expertise to review the research. If not, then they have to call on consultants to assist in the review. Researchers have the right under the regulations to have their research reviewed with the appropriate expertise and it is the Institutional Official's responsibility to ensure that the review is appropriate to the research.

Some IRB critics say that research should only be reviewed by people from the same field or let "ethnographers review ethnographers and experimental psychologists review experimental psychologists", as Zach Schrag has said. So, what's wrong with that? First of all, as noted above, the regulations require IRB members "with varying backgrounds". In addition, at §46.107(b), the regulations state "No IRB may consist entirely of members of one profession." Why? Because when IRBs are homogeneous they can become "blinded by the science". I have seen this happen many times on IRBs. The scientific members are focusing on the importance of the research and then a member from outside the field says, "Why is that so important? What about the impact on the subjects?". At that point, they other members say, "Oh, yeah. We forgot about that." Diversity of opinion helps ensure that all of the aspects of the research is taken into account.

Also, one aspect of human nature is that the more familiar we are about something, the more likely we are to underestimate the risks involved. It is very important to have input from people with diverse backgrounds to evaluate risk in research.

The strength of the IRB process is that it is a group decision-making process. I strongly believe that when a diverse group of people who understand the issues can come to a consensus, that is a close to a truly objective decision as is possible. After almost 30 years working with many IRBs, I have great faith in the system.

WHY HRPP?

2007-09-16T20:32:00.000-04:00

While helping client institutions prepare for AAHRPP site visits, one of the points I try to make is focused on the name of the organization - the Association for the Accreditation of Human Research Protection Programs. It is not the Association for the Accreditation of IRBs. That difference highlights the change in how we perceive what we do that has taken place over the past decade.

In the beginning, in the mid-70s when national attention first started being paid to research involving human subjects, it was thought that requiring IRB review of human subjects research would solve the problem of unethical research. For twenty years the task of protecting human subjects fell to IRBs and institutions felt that they had fulfilled their ethical responsibilities by having IRBs and requiring IRB review of research.

In the late 90s, two studies of the IRB system and a tragic event caused people to start questioning whether that was enough. The two investigations, one by the then Government Accounting Office and the other by the Inspector General of the Department of Health and Human Services, came to similar conclusions - the IRB system, in addition to being overburdened and under-resourced, was flawed and in need of revision. The system was too paper-driven and too "upfront". IRBs reviewed protocols but had no knowledge of what was happening after they approved the research. In addition, the federal regulatory agencies, especially the then Office for Protection from Research Risks, were also not monitoring what was really going on in the research world. Shortly after these investigations were published, Jesse Gelsinger died. His death, at one of the most prestigious research institutions in the country in an IRB-approved research study, also highlighted the flaws in the IRB system.

So, a lot of thought and discussion went into what was wrong with the system and what could be done to improve it. It was clear that IRB review was not enough to ensure ethical research. The IRB has a crucial role to play, but does not have sole responsibility for protecting subjects. The institution, through its policies and procedures, establishes an ethical framework for the conduct of research involving human subjects. The IRBs role is to provide independent, objective prior review of the research to ensure that the investigator has addressed all of the necessary ethical concerns in designing the research. Ultimately, it is the investigator who is responsible for the ethical conduct of the research.

What is required is an overall program of subject protection where responsibility was shared by the entire institution - an HRPP. An HRPP is a comprehensive and organized system to ensure the protection of human subjects participating in research. The HRPP is based on shared responsibility and accountability. It is only by having an effective HRPP that an institution can fulfill its ethical responsibility.

As someone who has been in this "business" for almost 30 years, I have seen this change take place and I sincerely believe that it is a change for the better. It is only through effective HRPPs that research institutions can fulfill their mission to advance human knowledge while meeting the highest ethical standards.

I'm Back

2007-09-01T19:44:00.000-04:00

Well, I'm back. Summer's over and it's time to get back to business with this blog. I will again try and post something every week and expect readers to nag me when I don't.

One thing that's changed is that I've had to add some spam barriers to the blog. Recently several spam comments were posted to the blog. Now I have to moderate the blog and screen for spam comments. I hope this isn't an inconvenience to anyone.

As we move into the Fall, I'd really like to hear from people who read the blog. I don't get many comments and, sometimes, it feels like I'm shouting down an empty well. From time to time I hear people mention the blog, but I'd really like to get some feedback. What kinds of topics would people like to see me address?

Regulations

2007-06-15T11:06:00.000-04:00

In light of the comments on my last post, I thought I'd post some of my thoughts about regulations. I have said most of this in the many presentations I've given on the regulations, but I thought I'd repeat them for this blog.

First of all, none of this (meaning human research protections) should be about complying with regulations. Now, I'm not saying you don't have to comply with the regulations. As a former fed, I'd be the last person to say that. You do have to comply with the regulations. But, that shouldn't be the primary focus of human research protections programs. The primary focus should be on doing it right because it is the right thing to do. Researchers have a moral and ethical responsibility to the subjects of their research and all research activities need an independent, objective review to help ensure that the research is done ethically. The primary focus of both the researchers and the IRBs should be on the ethics (along with the appropriate documentation to maintain accountablity). The good news is that, if researchers and IRBs focus on the ethics, they are most of the way there to complying with the regulations, since the regulations were designed to implement the ethical principles. The rest is just "dotting the i's and crossing the t's".

The second point I want to make is that the regulations are the floor, not the ceiling. The regulations establish minimum standards that must be followed with regard to human subjects research. Institutions are fee and should decide for themselves what the appropriate standards are for research conducted under their auspices, as long as those standards at least comply with the regulations.

Finally, as I said in my comment to Zach in the last post, I do not think that institutions should base their human subjects research policies on complying with the regulations. They should base their policies on how the institution has decided to fulfill its responsibility to the subjects because it's the right thing to do. In doing so, of course, the institution must commit to complying with all relevant federal, state, and local laws and regulations. In addition, I think that the decision making that goes into developing and adopting these policies should be an open and transparent process that includes input from all the stake holders (including investigators). In this way, no one at the institution can say, "Who are you to say I have to do this?"

The Mission of the IRB

2007-06-08T07:49:00.000-04:00

What is the mission of the IRB? If you ask most IRB members, the almost universal response will be that the mission is to protect human subjects. In my opinion, that is the wrong response. Seeing this as the mission of the IRB creates a "good guy/bad guy" mentality. It implies that research is a bad thing from which people need to be protected. Researchers are like Dr. Frankenstein and we are the villagers storming his castle with flaming torches to protect the public. In reality, research is a good thing. If we did not believe in the societal value of research, we would not be involved in the research enterprise. And, although there are a few "bad apples", the vast majority of researchers are good, well-intentioned people who would not dream of intentionally harming their subjects. In addition, this protectionist mission creates a mindset in IRB members where they look at each protocol thinking, "What are we going to find wrong with this one?"

Rather, the real mission of the IRB is to facilitate ethical research. As I said, research is a good thing and any unnecessary burdens or delays imposed on research has a social cost. That is not to say that IRBs should cut corners or be "rubber stamps". Research must be held to a high ethical (and regulatory) standard. But, IRBs should be focused on trying to help researchers do it right rather than catching them doing it wrong. IRB members should be thinking, "How can we help this good research go forward ethically?"

How can IRBs do this? For one thing, IRBs should keep in mind that every requirement that an IRB imposes on a researcher has a cost, either in time, paperwork, delay or even money. In the spirit of the Belmont principle of beneficence, IRB members should ask whether the benefits of imposing a requirement justify the cost to the investigator. Secondly, IRBs should work with investigators to explore options that meet the ethical and regulatory requirements without unduly interfering with the research. The IRB review process should be a dialog between the IRB and the investigators, with the common goal of the best research that meets the highest ethical standards.

Myths

2007-05-31T00:20:00.000-04:00

There are a lot of myths out there about IRB review. These myths are always being raised as fuel for the arguments of the IRB critics and, unfortunately, many IRBs succumb to these myths and provide "horror" stories for the critics. I'd like to debunk some of these myths in this posting.

The first is the myth that the ethical principles and the regulations require risk-free research. There is nothing in either that requires research to be risk free. What the regulations require are that 1) risks are minimized "by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk" [45CFR46.111(a)(1)] and 2) "Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result" [45 CFR 46.111(a)(2). The key concepts here are that research should not unnecessarily expose subjects to risk and that risks are reasonable in relation to benefits, including the benefit of acquiring knowledge. Subjects may be put at risk as long as there is sufficient benefit to justify the risk. I can't imagine any researcher who would put subjects at risk if there was no benefit to the knowledge being obtained or who would put subjects at more risk than is necessary to obtain the information that is needed.

The second myth is that the regulations require absolute confidentiality and, if possible, anonymity in research. Again, there is nothing in the ethical principles or the regulations that requires that. What the regulations say is "When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data" [45 CFR 46.111(a)(7). The key concepts here are "when appropriate" and "adequate provisions". Where confidentiality is not appropriate to the research, such as when the subjects want to be identified or the information is so innocuous that no reasonable person could care whether anyone knew what they said, then confidentiality is not required. In fact, the principle of Respect for Persons in the Belmont Report requires us to respect the wishes of the subjects with regard to confidentiality. On the other hand, the principle of informed consent requires us to make sure that the subjects understand what will happen to the information they provide and whether they will be identified.

Finally, there is the myth that signed, written consent forms are always required in research. Here, too, the regulations do not require consent forms in all research. The regulations, in 45 CFR 46.117(c), provide for a waiver of documentation of consent where the research is minimal risk and the research "...involves no procedures for which written consent is normally required outside of the research context." Interviews, survey, and questionnaires - the procedures most commonly used by social researchers - are done all of the time in the "real world" without signed consent forms, so, if they are minimal risk, they don't require signed consent forms in research. In fact, even if the research does not qualify for this waiver (e.g., more than minimal risk), the regulations provide for a "short form" procedure to document oral consent [45 CFR 46.116(b)(2).

So, IRBs that require risk-free procedures, absolute confidentiality or signed consent forms that invalidate the research are not complying with either the spirit or the letter of the regulations. Admittedly, IRBs are not as knowledgeable about how to use the flexibility in the regulations as they should be. Also, it is easier to apply strict, inflexible requirements than to consider how to apply the flexibility on a case-by-case basis. We need to continue and strengthen our efforts to educate IRBs on how to use the flexibility in the regulations.

Why not exempt social research?

2007-05-21T09:30:00.000-04:00

One of the major propositions that the critics of IRB review of social research put forth is that minimal risk social research with competent adults should be completely exempt from IRB review. On the surface, this makes some sense. We're talking about research that is unlikely to harm anyone and where adults can decide for themselves whether to participate. Why do we need to review such research? Based on my experience personally reviewing thousands of research protocols in the social sciences, there is one basic problem with this - researchers are human beings. Human beings are not perfect - they overlook things, make mistakes and and can't be totally objective about their own work. If researchers were perfect, if they always took all of the ethical issues into account when planning and conducting their research, then we wouldn't need IRB review. But they are not perfect - none of us are perfect. So, every research activity needs an independent, objective review.

That being said, IRBs are not perfect either. IRBs are made up of human beings as well. In my experience, IRB members often become hyper-critical when they review other researchers' protocols. They tend to drift into the mind set of "what are we going to find wrong with this one." IRB members have to keep reminding themselves that the IRB is not like a funding agency scientific review panel, they are not there to critique the research, but to make sure that the research is being done ethically. In fact, I often say that the mission of the IRB is not to protect human subjects but to facilitate ethical research. Every time they review a protocol they should be thinking "how can we help this good research go forward, ethically."

If researchers would recognize the necessity and value of the IRB review and IRB members (and administrators) would recognize that their mission is to help the researchers do it right rather than catch them doing it wrong, then a lot of the tension between IRBs and researchers would go away.

Appeals

2007-05-14T08:17:00.000-04:00

At a recent seminar held CUNY on IRBs and social/behavioral research, the question of an appeal process for IRB review was raised. This is an issue that has repeatedly been brought up as a criticism of the IRB process and I thought I’d address it.

First of all, the provision in the regulations that states, “…officials [of an institution] may not approve the research if it has not been approved by an IRB” [46.112] is there to minimize the influence of institutional conflicts of interest. If Dr. Smith, who has a multi-million dollar grant, complained to the President of the institution about an IRB decision and the President could overrule the IRB, then the protection of the subjects by the IRB process would be undermined. This decisional independence is essential for the IRB to fulfill its mission.That being said, IRBs are not autonomous entities unanswerable to anyone, as many critics claim. IRBs are agents of the institutions, which have the responsibility to ensure that the IRB process is not only in compliance with the regulations but also effective, efficient and appropriate to the research being reviewed. The FWA assigns that responsibility to the Institutional Official who signs the FWA.

So, while the institution cannot overrule negative decisions by the IRB, it can intervene if the process is inappropriate. This is similar to the US judicial system. The judicial appeal system does not rule on the outcome of trials, but on the process. You cannot appeal just because you disagree with the outcome of your trial, but you can appeal if you believe that you have been denied due process. Similarly, a researcher should not be able to appeal because he or she disagrees with the IRB’s decision. But, if he or she believes that the process was not fair, the decision was arbitrary or capricious, or did not have an appropriate ethical or regulatory basis, then the researcher has the right to appeal that to the Institutional Official. The IO should investigate the process and, if it is determined that the process was inappropriate, then the IRB should reconsider the decision.

In addition, the institution should oversee the IRB’s policies and procedures. The IRB should be responsible for explaining the basis for what it does and ensuring that its policies and procedures are appropriate for the research it reviews. How this is accomplished is up to the institution and depends on the culture and governance system at the institution. I strongly recommend that all institutions set up some sort of advisory committee for its HRPP. Again, this committee would not have any say over IRB decisions, but would have input on the IRB’s policies and procedures. The IRB should provide regular reports on its activities to this committee and the committee should review the HRPP policies and procedures. This would provide necessary transparency to the IRB review process and provide a voice for the concerns of the research community.

The perception that the IRB is not answerable to anyone undermines the research community’s trust in the IRB review process and could lead to an adversarial relationship between the IRB and the research community. Such an adversarial relationship puts subjects at risk because it increases the likelihood that researchers are not forthcoming to the IRB and that research is conducted without IRB approval.

Reinvigoration

2007-05-14T07:51:00.000-04:00

OK, what's the point of having a blog if you don't keep it up. This is what I've been hearing from a number of people, including my wife. I plead guilty as charged and now pledge to post to this blog on a weekly basis. In fact, if anyone sees that I have missed a week, please send me an email and remind me.

OHRP and Oral History

2006-11-28T08:23:00.000-05:00

At the PRIM&R conference in Washington last week I moderated a panel with Michael Carome and Julie Kaneshiro from OHRP on "When is it Human Subjects Research?" In his presentation, Dr. Carome finally clarified OHRP's position on oral history. As many of you know, in 2003 Dr. Carome wrote a letter stating that OHRP concurred with the position that oral history activities in general do not involve research as defined by the HHS regulations. Many oral historians took that to say that oral history was excluded from IRB review, including the Oral History Association. In his presentation at PRIM&R Dr. Carome clarified that this was meant in the same sense that drawing blood "in general" was not research. It is not the methodology that determines whether an activity is human subjects research, but whether it meets the regulatory definition of research - a systematic investigation designed to develop or contribute to generalizable knowledge. That is to say, the determination as to whether an oral history activity is human subjects research is based on how it is conducted and the purpose for which the activity was conducted. If an oral history activity meets the regulatory definition, it is human subjects research and, unless it is exempt, needs IRB review. This is what many of us have been saying all along.

The problem is that the regulations don't define "systematic investigation" or "generalizable knowledge" and they don't say who is to make that determination. As a result, it is up to institutions to come up with policies and procedures for making this determination. Both OHRP and AAHRPP expect institutions to have written policies and procedures for determining when an activity meets the definition of human subjects research. Here are my recommendations for how an institution should handle this:

1) It would be a mistake to allow investigators to make this determination on their own. It's not that they can't be trusted, but that they can't be totally objective about their own work. Since it is the institution that will be held accountable if they make the wrong decision, then the institution should provide for an independent, objective determination. On the other hand, this determination does not have to be made by the IRB. For exempt research, the OHRP guidance states that the determination should be made by a "knowledgeable" person or persons. The same should hold here. The determination could be made by someone from the IRB or IRB office, but could also be made by a trained departmental representative or committee. The training should be provided by the IRB staff and there should be a way to monitor the determinations if they are not made by outside reviewers.

2) The institution should develop clear definitions for "systematic investigation" and "generalizable knowledge". Here are the definitions from the generic policies and procedures that I have developed for my clients:

"For the purposes of this policy, a 'systematic investigation' is an activity that involves a prospective research plan which incorporates data collection, either quantitative or qualitative, and data analysis to answer a research question. Investigations designed to develop or contribute to generalizable knowledge are those designed to draw general conclusions (i.e., knowledge gained from a study may be applied to populations outside of the specific study population), inform policy, or generalize findings."

3) The institution should provide guidance on how to determine if an oral history activity meets this definition. The guidance should include examples of oral history activities that meet the definition and those that don't. I would recommend that this guidance be developed in conjunction with the oral historians at the institution.

4) For oral history activities that do meet the definition, I would strongly recommend that the IRB be trained on how to review oral history. Oral history and other qualitative research activities are different from the usual quantitative research reviewed by the IRB. I would suggest that the IRB bring in oral historians to provide training in oral history methodology and ethical issues.

5) When reviewing oral history research, the IRB needs to utilize the flexibility it has under the regulations to make its review appropriate to the research and not unduly burdensome on the historians. The IRB needs to use the exemptions and expedited review to minimize the time it takes for IRB review, develop submission forms appropriate to oral history projects, and utilize its waiver authority to make sure that the consent process is appropriate to oral history.

By working with the oral historians, providing clear guidance and using the flexibility in the regulations, an institution can come up with policies and procedures that provide appropriate

Accreditation

2006-08-20T08:38:00.000-04:00

As a consultant, I have been spending a lot of my time working with institutions on accreditation. I thought I’d share some of my general thoughts about accreditation on this blog.

First, let me say that I am a big fan of accreditation. I have worked with several institutions on accreditation over the past year and I think I can say, without reservation, that going through the accreditation process results in better human research protection programs. It does this in a couple of ways. First, preparing for accreditation forces an institution to examine its HRPP very closely. This often reveals gaps, inconsistencies and inefficiencies that creep into even the best programs. By committing to becoming accredited, institutions have to come up with ways to fix these problems. Second, accreditation forces institutions to have detailed, written policies and procedures for their HRPPs. Detailed policies and procedures help improve HRPPs in two ways: 1) they reduce the need for the IRB to make decisions on a case-by-case basis, and 2) they clearly inform investigators as to what is required to obtain IRB approval. Both of these help make an HRPP more effective and efficient.

That being said, I think many institutions go about the accreditation process the wrong way. Many institutions approach the accreditation process by trying to develop policies and procedures that address the elements of the accreditation standards. Not only do I think that this is the wrong way to develop policies and procedures, I also think that it hinders the accreditation process. My perception, which may or may not be shared by AAHRPP, is that the accreditation standards were not written to be a guide to the preparation of written HRPP policies and procedures, but as a tool for evaluating HRPPs (the document is even called an Evaluation Instrument). An institution’s written policies and procedures should be a working document that is used as a guide to the review and conduct of human subjects research, not something to get their HRPP accredited. Institutions should first make sure that they have the best HRPP they can have and write up policies and procedures that describe that program as clearly as possible. Then, they can go through the accreditation standards to make sure that all of the elements are addressed and, where necessary, modify the policies and procedures to better address the elements. Doing it the other way around results, I believe, in less usable policies and procedures. It also hinders and delays the accreditation process because it results in obsessing about what AAHRPP is looking for in each element. I’ve heard of institutions spending months and months, even years trying to do this. It is much more efficient to do it the way I suggested and then, during the accreditation process, let AAHRPP tell you where you might have missed the mark for a given element. Institutions should remember that they have ample opportunity to address deficiencies before a final accreditation decision is made. I also strongly recommend that institutions go through the preliminary application process. This allows you to address the deficiencies that AAHRPP identifies before you submit your final application.

People talk about accreditation the same way that people talk about going to the dentist, with fear and trepidation. Like with the dentist, it causes people to put off applying for accreditation (I’m using this analogy because my wife has been nagging about putting off going to the dentist for the past couple of months). If approached correctly, the accreditation process doesn’t have to be as aversive as people think and it can be a very positive experience (although they don’t give you a lollypop).

Student Research

2006-07-23T06:57:00.000-04:00

I thought I'd share my thoughts on student research since that's a topic that vexes IRBs, especially at universities. Most IRBs only review student research if it contributes to "generalizable knowledge" and, since most student research does not, most student research is not reviewed by IRBs. I believe that all student research, including undergraduate class projects, needs oversight to ensure that the rights and welfare of the subjects are adequately protected. I say this for two reasons. First, it doesn't matter to the subjects whether the person conducting the research is a student or a faculty member; their rights and welfare could still be at jeopardy. Second, the students lack of experience puts subjects at greater risk than faculty research.

Let me share an anecdote with you that illustrates my point. One day, when I was at Albany, a group of us were eating lunch on campus when a student came up to us and asked us if we'd answer some questions for a survey her class was conducting. Of course, I asked her if it had been approved by the IRB and who was her instructor (she had certainly come to the wrong table!). While she was standing there, another student, clearly from the same class, came over and asked her, "Do you know Joe over at the information desk? What until you hear what he said on the survey!" Now this was a fairly innocuous survey, but Joe's privacy had still be violated.

So, all student research needs ethical oversight. Can't the instructors provide that oversight since they are responsible for the research? I don't think so because they have a conflict of interest. In fact, they have two conflicts. The first conflict is a pedagogical one. They have an educational goal in assigning the research project and part of accomplishing that goal is keeping the students engaged. They might not want to limit the students' research for fear of discouraging them. The second conflict is temporal. They have an interest in getting the students done within a limited amount of time and would be disinclined to do anything which holds the student up. Like all human subjects research, all student research needs an independent, objective review.

I can already hear IRB people moaning how it's impossible for the IRB to take on that burden. Well, I can tell you that it doesn't have to been such a burden. This was our policy at Albany for the 20 years that I ran the IRB there and we were able to do it with a reasonable amount of work. First of all, we strongly encouraged all students to limit their research to exempt or expedited categories. We didn't require it, but told them that, if their research needed full review, they might not be able to complete the project on time. Second, we developed a three-tier system which helped facilitate the process. For projects where all of the students did the same thing or picked from a list of set projects, we had the instructor submit a protocol which detailed the project. This could be done before the class began. For projects where the students where designing their own research, either individually or in groups, we developed a one-page form for students to fill out which described their research. They submitted those along with any instruments they were using to the instructor who submitted them in an "umbrella" protocol for the whole class. Students conducting research which did meet the criterion of "generalizablity" or whose research did not qualify for exemption or expedited review had to submit their own protocols. I reviewed all of the student research and, even for classes in the second category with 75 or 100 students, I could review them in a few minutes. When reviewing those packets, we didn't hold up the whole class if some students needed more review. So, the burden is primarily on the expedited reviewer(s) and isn't a great burden at all.

Now, the good news is that, since student research doesn't meet the definition of research in the federal regulations, the detailed requirements of the regulations don't apply and institutions have a lot more flexibility in how they oversee student research. So, it doesn't have to be the IRB that does the review. An institution could use some sort of departmental review (as long as the reviewers are knowledgeable about human subjects issues) or, me favorite idea, a Student IRB. A Student IRB could be made up of advanced students, trained in human research protections, with an advisor from the IRB or the IRB office. This would be true peer review and would give the students on the IRB good experience and something valuable to put on their resumes. Actually, I think student reviewers would be tougher than the regular IRB. The University of Minnesota has a Student IRB, but I don't think it reviews class projects.

So, in conclusion, I think all student research needs ethical oversight. IRBs can provide this oversight without an undue burden, but institutions have other options for providing this oversight.

IRB Computer Systems

2006-06-06T19:12:00.000-04:00

In line with the purpose of this blog, which is to share my experience, I thought I'd discuss IRB computer systems. Let me make a couple of points up front. First of all, I am not going to talk about specific products or make product recommendations. As a consultant I will make recommendations regarding IRB computer systems to my clients, but I don't think I should do this on a public forum. Second, I do have a lot of expertise in this area. I developed my first IRB computer system in 1984! Yes, back in the dinosaur era of computers. The system I developed started in a program called Enable (probably one of the best computer systems ever), then in FoxPro and then in Access. I am in the process of developing a system in Access now for a client. I have also worked with a number of clients who have implemented or tried to implement some of the commercial systems on the market now. So, I do know something about IRB computer systems.

The first thing you need to keep in mind when considering IRB computer systems is the difference between IRB systems and most database systems. Most database systems are record-tracking and reporting systems. IRB systems are primarily communication systems. Although IRBs need to track protocols and occasionally produce reports, the most important function of an IRB system is to automate communcations - producing agendas, minutes, letters and other communications between the IRB and IRB members and investigators. These communication functions should be at the heart of any good IRB computer system and should be as automated and user-friendly as possible.

The second thing to keep in mind is that the system should be as customizable as possible. No two IRBs are the same and each one does things differently. The IRB should be able to tailor the system to meet its business practices. Customization should be easy and not require reprogramming the system. Ideally, the users should be able to customize the system themselves. IRB processes often change in response to new standards or best practices. If a computer system needs to be reprogrammed in order to incorporate minor changes, then it wil not meet the needs of an IRB.

Ideally, an IRB computer system, in addition to providing easily customizable administrative functions, should also provide for electronic submission and review of IRB protocols. Most investigators would be eager to submit their protocols electronically, but getting IRB members to electronically review protocols is a more difficult task. In addition to electronic protocol submission, a good system should also allow investigators to check on the status of their protocols themselves. This saves a lot of time for IRB staff.

I want to make two final points about IRB computer systems. First, I think a system you develop yourself is always better than purchasing a commercial system. As I said, no two IRBs are the same and no commercial system can do exactly what you want it to do. However, developing your own system take a long time and considerable expertise. The key to developing your own system is finding a computer person who understands or can be made to understand exactly what the IRB does and its needs. Second, I don't believe that "integrated systems" where Grants & Contracts, Tech Transfer, the IRB and IACUC are all in one system are necessary or desirable. These offices have very different functions and computer needs and making one system do it all often results in forcing square pegs in round holes. An integrated system is not necessary. These offices only need to share a limited amount of information and that information can be exported and imported between different system very easily these days.

A good IRB computer system that automates most of the clerical functions of the IRB can be the equivalent of .5 to 1 fte in IRB staff. By automating clerical functions, a good system can free up IRB staff to do less paper pushing and devote more time to working with investigators and doing administrative pre-review. This will result in expediting the review process and happier investigators. Note, however, that I said a "good system". A bad system can suck up IRB resources, both financial and human. There are good commercial systems out there, but you need take care in selecting a system that meets the needs of the IRB. It is also possible to develop a good system yourself, but it takes time and the appropriate expertise.

Apology

2006-06-06T07:30:00.000-04:00

I don't know how many people actually read this blog, other than those who have commented on it, but I owe you all an apology. A blog is not very useful if it is not updated regularly and I have been very lax in adding posts to this blog. One of the problems in being a consultant is that work goes in spurts and the last few weeks have been very busy for me. I'll try and make it a point to enter posts on a more regular basis from now on. If I don't, feel free to nag me about it. As many who know me well, I need a lot of nagging.

Signatures

2006-04-17T08:07:00.000-04:00

At a recent presentation I was asked about whether a witness' signature is required on consent forms. The requirements on signatures are so confusing, I actually misspoke myself. That prompted me to go back to the regulations and check what they actually say about signatures on consent forms. Each of the regulations (45 CFR 46, 21 CFR 50 and ICH E6) has different requirements for signatures. Here is a summary:

46.117(a) requires that the subject sign the consent form.

50.27(a) requires that the subject sign and date the consent form.

ICH 4.8.8 requires that the subjects and "the person who conducted the informed consent discussion" sign and date the consent form.

For oral presentations, all three require a witness to be present. 46.117(b)(2) and 50.27(b)(2) requires the subject to sign the short form. The witness signs both the short form and the summary of the information presented (usually the consent form) and the "person actually obtaining the consent" signs the summary. ICH 4.8.9 requires that the subject, if capable, and the witness sign and date the consent form. Only ICH explains what the witness is attesting to: "By signing the consent form, the witness attests that the information in theconsent form and any other written information was accurately explained to, and apparently understood by, the subject or the subject's legally acceptable representative, and that informed consent was freely given by the subject or the subject’s legally acceptable representative."

Now, the question is "Which one applies?" and the answer is "It depends". 45 CFR 46 applies to most federally funded research, 21 CFR 50 applies to research regulated by the FDA. Both regulations apply when either 1) federally-funded research involves an FDA-regulated product or 2) an institution has chosen to apply 45 CFR 46 to all of its research in its FWA. ICH is only guidance, not regulation. However, most industry-sponsored clinical trials are being conducted in compliance with ICH since the industry wants to market its products internationally.

In general, when deciding which regulations to apply, it is best to apply the most stringent. With regard to signatures on consent forms, ICH is most stringent and requires both the subject and the person obtaining consent to sign and date the consent form. For oral presentations, the FDA is the most stringent, requiring the subject and the witness to sign a "short form" and the witness and person obtaining the consent to sign the consent form.

Caution on "unchecking the box"

2006-04-16T07:44:00.000-04:00

I have to add a note of caution on my comments on "unchecking the box" to limit an FWA to federally-funded research. Before you do that, make sure that this does not affect the application of state or local laws. It was recently brought to my attention that, in New York, if the FWA doesn't apply to non-federally funded research, then the New York human subjects law (Article 24-A of the Public Health Law) would apply to that research. So, New York institutions should carefully consider whether they should "uncheck the box". My recommendation regarding only applying the Common Rule (without the subparts) still applies, though. The research would still be covered by federal regulations but not the subparts.

IRB Independence

2006-04-05T14:54:00.000-04:00

I recently participated in a discussion on the IRBForum regarding the involvement of the Institutional Official (IO) in the policies and procedures of the IRB. This prompted me to expand on my thoughts here.

Many people believe that the IRB must be a completely autonomous body that operates without any interference from the institution. I not only believe that this is a mistaken interpretation, but it is also dangerous and puts subjects at risk. The independence required for the IRB to fulfill its mission is independence in decision making. In Sections 112 of 45 CFR 46 and 21 CFR 56 the regulations state that institutional officials cannot approve research if it has not been approved by the IRB. Thus maintaining the independence of IRB decisions, at least negative decisions. This is not saying that IRBs are completely independent from the institution. In fact, Section 112 also says that research approved by the IRB can be subject to further review by the institution. The assurance process in 45 CFR 46 gives the responsibility for establishing policies and procedures for the protection of human subjects to the institution. Therefore, it is the institution, generally through the IO, which sets policy, not the IRB. So, the belief that the IRB is completely independent is mistaken.

Why is this belief dangerous? Because a completely independent IRB runs the risk of having an adversarial relationship develop with the investigators. Without some oversight over its policies and procedures, the IRB can wind up losing sight of the burden that its requirements place on investigators. When that happens (and I have seen it develop several times as a consultant), an adversarial relationship can develop between the IRB and the investigators. This type of relationship increases the chances that investigators will not be forthcoming with the IRB or will even conduct research without IRB approval. This is when subjects are put at risk.

This is not to say that IRBs should become "rubber stamps" or that institutional polices and procedures should be lax. Rather, that the institution has the responsibility to ensure that the policies and procedures of the IRB are reasonable. As I said in the discussion on the IRBForum, the IRB needs to follow the principle of beneficence, similar to that in the Belmont Report, in its relations with investigators. It needs to make sure that the benefits of imposing requirements on investigators (primarily in terms of protecting subjects) justify the cost (in time, money, paperwork, etc.) to the investigators.

So, I do believe that the IO must be involved with the way that the IRB performs its function. The IO cannot and should not intervene in IRB decisions, but should oversee the policies and procedures that govern how the IRB functions and ensure that they balance the need to protect subjects with the needs of the investigators.

The Short Form

2006-03-28T22:14:00.000-05:00

Recently, some colleagues and I had a discussion about the "short form" for documenting consent. As most of you know, the federal regulations allow the use of "A short form written consent document stating that the elements of informed consent required by [§46.116/>50.25] have been presented orally to the subject or the subject's legally authorized representative." [46.117(b)(2)/50.27(b)(2)] The short form may be used when the subject does not speak English or another language where there is a translated consent form. It may also be used when the subject is illiterate.

The short form is not used very much and many institutions don't use it all. This is probably because most people don't understand it and are afraid to use it. The problem is that there is not much guidance out there on the use of the short form. The only OHRP guidance on this is from 1995 (http://www.hhs.gov/ohrp/humansubjects/guidance/ic-non-e.htm) but I guess it still applies. It says that the short form should be in the subject's native language. It also says: "The IRB must receive all foreign language versions of the short form document as a condition of approval under the provisions of §46.117(b)(2). Expedited review of these versions is acceptable if the protocol, the full English language informed consent document, and the English version of the short form document have already been approved by the convened IRB."

I believe that IRBs should not be afraid to use the short form where it is appropriate since it is allowed in the regulations. The appropriate use is for subjects who speak an unanticipated language. If there is a reasonable expectation that there will be subjects recruited for the research who speak a certain language (most commonly, Spanish), then the consent form should be translated into that language. The short form should not be used in that case.

The problem is OHRP's guidance which requires IRB approval of the short form which should be in the subject's language. Although this can be done through expedited review, it can still be burdensome. This makes the use of the short form problematic for the situation where a subject shows up who speaks an unanticipated language. This, however, is guidance from OHRP and old guidance at that. I think an IRB could make a good case that the regulations do not require IRB approval of the short form or that the short form be in the subject's language. If a witness signs the short form indicating that the information in the English consent has been provided to the subject in his or her native language and that the subject consented to be in the research, that should be satisfactory documentation of informed.

I hope that OHRP comes up with new guidance on this topic and reconsiders the requirements of the old guidance. FDA guidance (http://www.fda.gov/oc/ohrt/irbs/informedconsent.html#nonenglish) does not require IRB approval or that the short form be in the subject's language.

Mission Creep

2006-03-04T10:14:00.000-05:00

The other day I was asked to comment on the "Mission Creep" white paper. The paper recommends "...focusing on those areas of research that pose the greatest risk, such as biomedical research, while removing or reducing scrutiny of many fields within the social sciences and humanities that pose minimal risk." This is based on the assumption that the primary purpose of IRB review is to protect subjects from risk. Beneficence, which addresses the relation between risk and benefit, is only one of the three Belmont principles. There are respect and justice issues even in minimal risk, innocuous research. I believe that all research activity, even innocuous research, requires some sort of independent, objective review. Reducing the oversight over minimal risk research jeopardizes

The problem that this paper is responding to is not IRB review per se, but IRB review that is unduly burdensome and that imposes unreasonable requirements. So, while claims that IRB review is not necessary for minimal risk research are not reasonable, IRBs are somewhat responsible for the attacks on IRB review. I have long argued that the regulations provide sufficient flexibility for the efficient and appropriate review of minimal risk research. IRB review of such research does not have to be burdensome or unreasonable if IRBs appropriately utilize the flexibility in the regulations. The horror stories that social and behavioral researchers quote in their attacks on IRB review are true. I have seen institutions where expedited review takes longer than full review and where IRBs have imposed written consent forms on telephone interview research. These are IRBs that a) don't understand social and behavioral research, b) don't know how to use or are afraid to use the flexibility in the regulations, and c) don't pay sufficient attention to the efficiency of their procedures.

The White Paper correctly recommends that IRBs receive better guidance on how to review non-biomedical research and that there needs to be increased sharing of best practices among IRBs. However, critics of IRB review should focus their attention on educating IRBs on the appropriate review of non-biomedical research rather than trying to reduce IRB oversight of such research.

Prisoner consent question

2006-03-04T10:08:00.000-05:00

Recently I was giving a talk about prisoner research and had discussed OHRP's guidance on subjects who become incarcerated after enrolling in a research study. Someone from the audience asked me about what happens if a legally authorized representative who has consented on behalf of a subject becomes incarcerated. This was something I hadn't thought about and I doubt whether there is any guidance on it. My take on it was that, as long as consent had been appropriately obtained, there is no problem with the LAR being incarcerated. The requirements of Subpart C only apply to the subjects, not the LARs. However, if the subject needs to be re-consented there is a problem. I'm not sure if it's appropriate for an incarcerated LAR can give consent for a subject. On the other hand, the regulations don't address this, so I don't think there is a rule against it. I guess, before approving consent from an incarcerated LAR, I'd contact OHRP and get their opinion about it.

IRB Roster Question

2006-02-16T08:04:00.000-05:00

Well, I've been in this business for 27 years and I thought I'd heard everything, but this is something new. An IRB member informed an IRB administrator that he was going to be changing his name -- from John to Joan!! Does that have to be reported to OHRP as a roster change?? What, exactly, are the criteria for the sex of an IRB member? Cross dressing, transgender, transsexual, pre-op, post-op???? I suggested that they call OHRP for guidance. I'd love to be there when they do!

Checking the Box

2006-02-07T16:15:00.000-05:00

As some of you know, for many years I was a major proponent of institututions applying the Federal-Wide Assurance (FWA) to all research regardless of funding. I have recently changed my position on that and now recommend that that institutions limit their FWA to federally-funded research. Here are some of my thoughts as to why I've taken that position.

All institutions engaged in human subjects research that is not exempt from the regulations, and is conducted or supported by any federal department or agency that has adopted the Common Rule must be covered by an OHRP-approved assurance of compliance.The form for applying for a FWA presents institutions with the option of voluntarily applying either the Common Rule or the Common Rule and subparts B, C, and D of the HHS regulations at 45 CFR 46 to all research, regardless of source of support. Institutions indicate with an [x] which, if any, of the options they chose to elect.The question is whether institutions should “check the box” or only have their FWA apply to federally-funded research.

First of all, except for FDA-regulated research, the federal government has no authority to regulate non-federally-funded research.In the past, OHRP strongly encouraged institutions to apply their FWA to all research, but this was a recommendation only.The reason for this recommendation was that most institutions had no formal policy on human subjects research and the only institutional authority for the IRB to review human subjects research was the FWA.Therefore, unless the FWA applied to all research regardless of funding, the IRB had no authority to review non-federally-funded research.This could result in a double standard with federal regulations applying to federally-funded research and a different standard, or no standard, applying to non-federally-funded research.Officials from OHRP have informally agreed that, if an institution has an institutional policy at least equivalent to the federal regulations that applies to all human subjects research, there is no need to apply the FWA to all research.

Although applying the FWA to all research may not be required, the question remains as to what harm would be done by “checking the boxes”.The basic problem with applying the FWA to all research is that it gives OHRP oversight over all of the research conducted by the institution.By limiting the FWA to federally-funded research, OHRP’s oversight is similarly limited.When problems arise with non-federally-funded research it is the institution’s responsibility to deal with and OHRP has no authority to intervene.Let me give you an example of how OHRP oversight over non-federally-funded research can be a problem for an institution.OHRP received a complaint regarding some research at an institution which had elected to apply the FWA to all research.The research in question was primarily chart-review research which was not federally funded.Because they had “checked the box”, OHRP did an investigation and the institution spent considerable time and effort to respond.After several months and considerable institutional stress and anxiety, OHRP terminated their investigation but reserved the right to conduct a site visit in the future.If the institution had limited its FWA to federally-funded research OHRP would have had no authority to investigate this research and all of this could have been avoided.

In addition, at least one part of the federal regulations (Subpart B: Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research) has language which makes it difficult to apply to social and behavioral research. Therefore, applying the FWA to all research creates inherent compliance problems for that research.

So, if an institution has a strong institutional policy that applies to all human subjects research regardless of funding, then, in my opinion, it should not apply the FWA to all research. This is in the institution's best interest and, if the institutional policy is adequate, does not diminish the protection of human subjects.

Been There, Done That

2006-02-07T08:39:00.000-05:00

For those of you who don't know me, I thought I'd introduce myself. Like the title of this posting says, I've "been there, done that" with regard to HRPPs. I started out as a researcher and teaching research methodology in Psychology. I then was an IRB administrator for twenty years (I started on month after the Belmont Report was published - May 1979). After that I was a "fed", serving as Director of Education at OHRP for four years. For two years I was an Institutional Official at a medical school and I am now an independent consultant in human research protections. So, I've seen it from all sides and I'm still seeing new things in this field.

Why a blog?

2006-02-06T16:53:00.000-05:00

Why am I posting a blog about HRPPs? Basically, to share my experience with human research protection programs more broadly. I often get asked for advice on HRPPs and, as a consultant, I give advice to my clients. Aside from occasional postings on the IRB Forum, this advice only goes to a small number of people. After reading about blogs and how, with a minimal amount of effort, information can be shared broadly, it seemed like a good way to reach more people. So, here I am with a blog on HRPPs. Whenever I get asked for advice, I will try and post my response here. I will also, from time to time, post general thoughts or comments on HRPPs here. Please feel free to comment - I don't have all of the answers!